This invention relates to therapeutic agents for use in the treatment of mammalian, particularly human, autoimmune diseases. The invention also relates to therapeutic agents useful in the treatment of human leukaemias of a T cell origin, as so-called "vaccine carriers", and as agents for use in the prevention of human transplantation rejection and graft versus host disease (GVHD).
In an article entitled "Morphologic and Functional Alterations of Mucosal T Cells by Cholera Toxin and its B subunit" by Charles O. Elson et al., The Journal of Immunology, 1995, 154; 1032-1040 it is disclosed that the cholera toxin (Ctx) and the CtxB subunit inhibit CD8.sup.+ and CD4.sup.+ T cells.
Reference is also made to the paper entitled "Prevention of Acute Graft-Versus-Host Disease by Treatment with a Novel Immunosuppressant" by B. Yankelevich et al., The Journal of Immunology, 1995, 154: 3611-3617. This identifies CtxB as an agent for use in bone marrow transplantation for the prevention of acute graft-versus-host disease (GVHD).
WO 95/10301 discloses an immunological tolerance-inducing agent comprising a mucosa-binding molecule linked to a specific tolerogen.
As used herein, the term "Ctx" refers to the cholera toxin and "CtxB" to the B subunit of the cholera toxin. In other texts, these may sometimes be identified as "CT" or "Ct" and "CTB" or "CtB" respectively. The term "Etx" herein means the E. coli heat labile enterotoxin, and "EtxB" is the B subunit of Etx. In other texts, these may sometimes be identified as "LT" or "Lt" and "LTB" or "LtB" respectively.
The basis for all aspects of the present invention is the finding that EtxB (the pure B-subunit of the E. coli heat labile enterotoxin) binds to GM1-ganglioside receptors which are found on the surfaces of mammalian cells, and that this binding induces differential effects on lymphocyte populations, including a specific depletion of CD8.sup.+ T cells and an associated activation of B cells. These effects are absent when a mutant EtxB protein lacking GM1 binding activity is employed.
Autoimmune Disease
Autoimmunity is the term used to describe the mechanism by which the body generates an immune response to self-antigens.